theophylline-salicylic acid | 41107-90-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: theophylline-salicylic acid
• 英文别名: Theophylline-salicylic acid cocrystal；1,3-dimethyl-7H-purine-2,6-dione;2-hydroxybenzoic acid
• CAS: 41107-90-8
• 化学式: C₇H₆O₃*C₇H₈N₄O₂
• 分子量: 318.289
• InChiKey: QYKYRTZZAWAKFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.05
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  茶碱 、 水杨酸 以 乙腈 为溶剂， 生成 theophylline-salicylic acid
  参考文献：
  名称：

  由茶碱和羟基苯甲酸组成的晶体形式的合成子层次：通过溶液介导的相变的共晶筛选

  摘要：

  使用九种（二）羟基苯甲酸作为共晶形成剂，即2-，3-，4-羟基苯甲酸和2,3-，2,4-，2,5-，筛选茶碱类药物模型化合物的共晶形成，2,6-，3,4-和3,5-二羟基苯甲酸。实验是基于热力学驱动的溶液介导的相变，使用高效，可靠和快速的筛选方法进行的，揭示了八种共晶体和一种盐的形成。使用粉末鉴定基于茶碱的固体，并通过单晶X射线衍射对其结构进行表征。除了茶碱和羧酸均合成子以外，所获得的固体还通过茶碱-羧酸杂合成子维持。结果是对黄嘌呤生物碱共晶体的系统研究的一部分，该研究旨在在由具有多个氢键官能团的分子组成的共晶体中建立合成子层次。讨论了结构特征和合成子层次，并将其与一系列已发布的咖啡因共晶体中的结构特征和合成子层次进行了比较。

  DOI：

  10.1021/cg501204k

文献信息

• Assessment of Co-sublimation for the Formation of Multicomponent Crystals
  作者：Jean Lombard、Delia A. Haynes、Tanya le Roex

  DOI：10.1021/acs.cgd.0c01148

  日期：2020.12.2

  The merits of co-sublimation and mechanochemistry as screening techniques for multicomponent crystal formation are compared. Several multicomponent crystals that can be formed both mechanochemically and by sublimation are investigated, allowing for a comparison between the relatively unknown technique of co-sublimation and a well-known, robust solid-state screening methodology. This work aims to determine the general utility and versatility of co-sublimation in the preparation of multicomponent crystals. Co-crystals and salts, as well as their polymorphs, have been investigated, and problems that can arise due to sublimation temperature differences, isomerization, and degradation are discussed. Co-sublimation is shown to be a valuable co-crystallization technique for the discovery and identification of new multicomponent materials.

  比较了共升华和机械化学作为多组分晶体形成筛选技术的优点。研究了几种既能通过机械化学又能通过升华形成的多组分晶体，从而对相对未知的共升华技术和众所周知的稳健固态筛选方法进行了比较。这项工作旨在确定共升华法在制备多组分晶体方面的一般实用性和多功能性。研究了共晶体、盐及其多晶体，并讨论了由于升华温度差异、异构化和降解可能产生的问题。研究表明，共升华是发现和鉴定新型多组分材料的一种重要共结晶技术。
• Pharmaceutical co-crystal compositions
  申请人：Almarsson Orn

  公开号：US20070026078A1

  公开（公告）日：2007-02-01

  A pharmaceutical composition comprising a co-crystal of an API and a co-crystal former; wherein the API has at least one functional group selected from ether, thioether, alcohol, thiol, aldehyde, ketone, thioketone, nitrate ester, phosphate ester, thiophosphate ester, ester, thioester, sulfate ester, carboxylic acid, phosphonic acid, phosphinic acid, sulfonic acid, amide, primary amine, secondary amine, ammonia, tertiary amine, sp2 amine, thiocyanate, cyanamide, oxime, nitrile diazo, organohalide, nitro, s-heterocyclic ring, thiophene, n-heterocyclic ring, pyrrole, o-heterocyclic ring, furan, epoxide, peroxide, hydroxamic acid, imidazole, pyridine and the co-crystal former has at least one functional group selected from amine, amide, pyridine, imidazole, indole, pyrrolidine, carbonyl, carboxyl, hydroxyl, phenol, sulfone, sulfonyl, mercapto and methyl thio, such that the API and co-crystal former are capable of co-crystallizing from a solution phase under crystallization conditions.

  一种药物组合物，包括API和共晶形成剂的共晶体；其中，API具有至少一种从醚，硫醚，醇，硫醇，醛，酮，硫酮，硝酸酯，磷酸酯，硫代磷酸酯，酯，硫酯，硫酸酯，羧酸，膦酸，亚磷酸，磺酸，酰胺，一级胺，二级胺，氨，三级胺，sp2胺，硫氰酸盐，氰胺，肟，腈，重氮，有机卤化物，硝基，s-杂环环，噻吩，n-杂环环，吡咯，o-杂环环，呋喃，环氧化物，过氧化物，羟肟酸，咪唑，吡啶中至少一种官能团，而共晶形成剂具有至少一种从胺，酰胺，吡啶，咪唑，吲哚，吡咯烷，羰基，羧基，羟基，酚，磺酰，磺酰基，巯基和甲硫基中选择的官能团，使得API和共晶形成剂能够在结晶条件下从溶液相共结晶。
• Pharmaceutical Co-Crystal Compositions
  申请人：Almarsson Orn

  公开号：US20100311701A1

  公开（公告）日：2010-12-09

  A pharmaceutical composition comprising a co-crystal of an API and a co-crystal former; wherein the API has at least one functional group selected from ether, thioether, alcohol, thiol, aldehyde, ketone, thioketone, nitrate ester, phosphate ester, thiophosphate ester, ester, thioester, sulfate ester, carboxylic acid, phosphonic acid, phosphinic acid, sulfonic acid, amide, primary amine, secondary amine, ammonia, tertiary amine, imine, thiocyanate, cyanamide, oxime, nitrile diazo, organohalide, nitro, S-heterocyclic ring, thiophene, N-heterocyclic ring, pyrrole, O-heterocyclic ring, furan, epoxide, peroxide, hydroxamic acid, imidazole, pyridine and the co-crystal former has at least one functional group selected from amine, amide, pyridine, imidazole, indole, pyrrolidine, carbonyl, carboxyl, hydroxyl, phenol, sulfone, sulfonyl, mercapto and methyl thio, such that the API and co-crystal former are capable of co-crystallizing from a solution phase under crystallization conditions.

  一种药物组合物，包括API和共晶形成剂的共晶体；其中API具有至少一种功能基团，所述功能基团包括醚、硫醚、醇、巯基、醛、酮、硫酮、硝酸酯、磷酸酯、硫代磷酸酯、酯、硫酯、硫酸酯、羧酸、膦酸、亚磷酸、磺酸、酰胺、一级胺、二级胺、氨、三级胺、亚胺、硫氰酸盐、氰胺、肟、腈、重氮、有机卤化物、硝基、S-杂环环、噻吩、N-杂环环、吡咯、O-杂环环、呋喃、环氧化物、过氧化物、羟肟酸、咪唑和吡啶；共晶形成剂具有至少一种功能基团，所述功能基团包括胺、酰胺、吡啶、咪唑、吲哚、吡咯烷、羰基、羧基、羟基、酚、磺酰、磺酰基、巯基和甲基硫，因此，在结晶条件下，API和共晶形成剂能够从溶液相共结晶。
• PHARMACEUTICAL CO-CRYSTAL COMPOSITIONS OF DRUGS SUCH AS CARBAMAZEPINE, CELECOXIB, OLANZAPINE, ITRACONAZOLE, TOPIRAMATE, MODAFINIL, 5-FLUOROURACIL, HYDROCHLOROTHIAZIDE, ACETAMINOPHEN, ASPIRIN, FLURBIPROFEN, PHENYTOIN AND IBUPROFEN
  申请人：Transform Pharmaceuticals, Inc.

  公开号：EP1608339A1

  公开（公告）日：2005-12-28
• PHARMACEUTICAL CO-CRYSTAL OF CELECOXIB-NICOTINAMIDE
  申请人：McNEIL-PPC, Inc.

  公开号：EP1608339B8

  公开（公告）日：2012-04-25